(1) Field of the Invention
The present invention relates to a pyrazino[2,3-d]isoxazole derivative that is useful as a production intermediate or the like of 6-fluoro-3-hydroxy-2-pyrazine carboxamide (hereinafter referred to as “T-705”) useful for treatment such as prevention and therapy of influenza virus infection, and a method for producing the same. In addition, the present invention relates to a method for producing a pyrazinecarbonitrile derivative and a pyrazinecarboxamide derivative using the pyrazino[2,3-d]isoxazole derivative.
(2) Description of Related Art
T-705 is a compound useful for the prevention, treatment and the like of virus infection, and particularly, influenza virus infection. It has been known that T-705 is produced from, for example, 6-fluoro-3-hydroxy-2-pyrazinecarbonitrile (hereinafter referred to as T-705A) (Patent Documents 1 and 2). Patent Document 2 describes that T-705A can be efficiently isolated in the form of salts with various amines.
Examples of a known production method of T-705A includes: (1) a method comprising allowing 3,6-difluoro-2-pyrazinecarbonitrile to react with benzyl alcohol and then debenzylating the reaction product; (2) a method comprising allowing 3,6-difluoro-2-pyrazinecarbonitrile to react with water; and (3) a method comprising allowing 3,6-difluoro-2-pyrazinecarbonitrile to react with carboxylate and then generating T-705A by hydrolysis (Patent Documents 1 and 2).
However, since 3,6-difluoro-2-pyrazinecarbonitrile has high skin irritancy, and easily vaporizes due to low-molecular-weight liquid, it has had a manufacturing problem in that it requires special equipment and careful handling.
Moreover, with regard to the synthesis of pyrazino[2,3-d]isoxazole having a carbonyl group at position 3, examples described in Non-Patent Documents 1 and 2 have been known. However, the pyrazino[2,3-d]isoxazole of the present invention cannot be synthesized by such synthetic methods.